NAV 3 is a
tumor suppressor of unknown function in
leiomyomas. The objective of this study is to assess NAV3 expression and its potential role in human uterine
leiomyomas. NAV3
protein expression was examined in patient
leiomyoma and patient-matched myometrial tissue samples by Western blot and immunohistochemistry. NAV3
mRNA and
protein expression was assessed in
leuprolide acetate- and
cetrorelix-treated cell line
leiomyoma samples. RNAseq analysis of placebo-treated
leiomyoma compared with myometrium demonstrated the presence of transcripts encoding for several neuronal
proteins. For NAV3, RNA sequence analysis demonstrated decreased expression in
leiomyoma as compared with myometrium (0.86 ± 0.03 fold). Presence of NAV3
mRNA was also decreased in
leiomyoma surgical samples (0.43 fold ± 0.05, p = 0.026) compared with patient-matched myometrium. Confirmatory qRT-PCR results on immortalized
leiomyoma and myometrial cell lines similarly demonstrated a decrease in expression of NAV3 in
leiomyomas (0.28 ± 0.02, p = 0.00075). Immunohistochemical analysis demonstrated a significant decrease in NAV 3
protein in
leiomyomas (H-score 154.7 ± 6.2) as compared with myometrium (H-score; 312.5 ± 14.7, p < 0.0001).
Leuprolide acetate-treated
leiomyoma cells demonstrated an increase in NAV 3
mRNA expression (1.53 ± 0.13, p < 0.0001). Similarly, Western blot analysis on
leuprolide-treated
leiomyoma cells showed a non-significant increase in NAV 3
protein expression (1.26 ± 0.09, p = 0.063). NAV 3, a
tumor suppressor in numerous
cancers, is decreased in
leiomyoma cells and tissue compared with myometrium, and increased by
GnRH analog treatment, suggesting that NAV3 may mediate
steroid hormone-independent
leiomyoma regulation by
GnRH analogs.